Wang Wenzhao, Wang Shanxi, Zhang Zhengdong, Li Jun, Xie Wei, Su Yanlin, Chen Jianan, Liu Lei
Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.
Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;Department of Orthopedics, the Second People's Hospital of Jiulongpo District, Chongqing, 400050, P.R.China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2020 Feb 15;34(2):213-219. doi: 10.7507/1002-1892.201905079.
To systematically profile and characterize the circular RNA (circRNA) and microRNA (miRNA) expression pattern in the lesion epicenter of spinal tissues after traumatic spinal cord injury (TSCI) and predict the structure and potential functions of the regulatory network.
Forty-eight adult male C57BL/6 mice (weighing, 18-22 g) were randomly divided into the TSCI ( =24) and sham ( =24) groups. Mice in the TSCI group underwent T vertebral laminectomy and Allen's weight-drop spinal cord injury. Mice in the sham group underwent the same laminectomy without TSCI. The spinal tissues were harvested after 3 days. Some tissues were stained with HE staining to observe the structure. The others were used for sequencing. The RNA-Seq, gene ontology (GO) analysis, and circRNA-miRNA network analyses (TargetScan and miRanda) were used to profile the expression and regulation patterns of network of mice models after TSCI.
HE staining showed the severe damage to the spinal cord in TSCI group compared with sham group. A total of 17 440 circRNAs and 1 228 miRNAs were identified. The host gene of significant differentially expressed circRNA enriched in the cytoplasm, associated with positive regulation of transcription and protein phosphorylation. mmu-miR-21-5p was the most significant differentially expressed miRNA after TSCI, and circRNA6730 was predicted to be its targeted circRNA. Then a potential regulatory circRNA-miRNA network was constructed.
The significant differentially expressed circRNAs and miRNAs may play important roles after TSCI. A targeted interaction network with mmu-miR-21-5p at the core of circRNA6730 could provide basis of pathophysiological mechanism, as well as help guide therapeutic strategies for TSCI.
系统分析和表征创伤性脊髓损伤（TSCI）后脊髓组织损伤中心的环状RNA（circRNA）和微小RNA（miRNA）表达模式，并预测调控网络的结构和潜在功能。
48只成年雄性C57BL/6小鼠（体重18 - 22 g）随机分为TSCI组（n = 24）和假手术组（n = 24）。TSCI组小鼠行T10椎体椎板切除术及Allen's重量坠落法脊髓损伤。假手术组小鼠行相同椎板切除术但不进行TSCI。3天后采集脊髓组织。部分组织进行HE染色观察结构。其余组织用于测序。采用RNA-Seq、基因本体（GO）分析和circRNA-miRNA网络分析（TargetScan和miRanda）来分析TSCI后小鼠模型网络的表达和调控模式。
HE染色显示TSCI组脊髓损伤较假手术组严重。共鉴定出17440个circRNA和1228个miRNA。显著差异表达的circRNA的宿主基因富集于细胞质，与转录的正调控和蛋白质磷酸化相关。mmu-miR-21-5p是TSCI后差异表达最显著的miRNA，circRNA6730被预测为其靶向circRNA。随后构建了一个潜在的调控circRNA-miRNA网络。
显著差异表达的circRNA和miRNA可能在TSCI后发挥重要作用。以circRNA6730为核心、mmu-miR-21-5p为靶点的相互作用网络可为TSCI的病理生理机制提供依据，并有助于指导其治疗策略。
